Field of the Invention
This invention pertains to compositions, and methods of using the same, to protect mammals from, and treat mammals with diseases and conditions, mediated by various agents, including disease agents, heavy metals and other substances that can be bound by surface interaction with low molecule weight pectinates and alginates.
It is well known that gelling agents may be effective in binding to a variety of substances, in vitro. While high molecular weight binding substances are known, it is difficult for such substances to pass various blood barriers, including the gut, and circulate freely in the bloodstream. Their solubility in water is generally too low to permit in vivo utility of any kind.
Cancer metastasis is a stage of cancer which frequently marks conversion to an incurable disease. Most cancers share the ability to metastasize. This application has applicability to all metastatic cancers. In the metastatic process, cells depart from the primary tumor, invade the basement membrane, traverse the bloodstream as tumor cell emboli and interact with the vascular endothelium of the target organ. There, they proliferate to form secondary colonies. Kohn, Anti-Cancer Res., 13:2553-2259 (1993). It has been demonstrated that modified citrus pectin, administered orally, may be effective in suppressing or preventing metastases, by binding to residues on the cell surface, presumably through galactosyl residues in the modified (low molecular weight) pectin, perhaps through surface galectin-3. Pienta, et al., J. Nat. Cancer Inst. 87, 348-353 (1995).
Cancer is not the only inimical element circulating in mammalian blood streams, however, and in many cases, cancer is mediated by inorganic agents present. Thus, heavy metals and minerals, such as calcium, can induce arteriosclerosis, which is also influenced by the presence of cholesterol in the bloodstream. While there are a variety of treatments for elements such as heavy metals, typically, these embrace removal of portions of the blood supply, and treatment of the same.
Pectin, or pectinates, digestion products of pectin, are generically known as gelling agents, as are alginates. Alginates occur naturally, and a chief source is seaweeds. Alginates are formed by a mixture of polymannuronic acid and polyguluronic acid. Repeating sub-units are bound by glycosidic links at the 1a-4a-di-axial position (polyguluronic acid) while repeating sub-units of polymannuronic acid are bound by galactic links at the 1e-4e di-equatorial position. Like pectins, naturally occurring algins are high molecular weight products. They can, however, be reduced to low molecular weight products (defined herein as 40,000 daltons or less) by either chemical treatment (alkaline hydrolysis) or enzymatic degradation. Alginates generally have superior protein recovery rates when compared to pectinates of relatively similar molecular weight. Clare, Industrial Gums (1993 3.sup.rd Edition) and therefor exhibit a stronger ability than pectinates to bind with galectin 3, the carbohydrate binding protein on the surface of cancer cells.
A wide variety of seaweeds, which include algins, as well as the alginic constituent components, have been used in studies treating cancer. See, e.g., Itoh, Anti-Cancer Res. Sept.-Oct. (1995) and Kitasato, Archives of Exp. Med., 1987. In general, these studies and recommendations focus on various polysaccharide constituents such as fucoidan, which exhibits anti-tumor activity, but do not report the utility of alginates in preventing cell adhesion, or otherwise suppressing metastatic events. Low molecular weight alginates have been associated with the reduction of cholesterol in softdrinks, and alginate-coated sheets have been employed for the manufacture of a prototype artificial pancreas. Islet Medical, Feb., 1998. Transplants coated with alginates have also been used in the treatment of diabetes. There does not appear to be a report, however, of the use of low molecular weight alginates as opposed to pectins in the prevention or treatment of metastasis. Because of the superior recovery rate associated with alginates, it would be of value to be able to use alginates for this purpose.
Besides binding cancer cells, alginates are known to be effective metal binding compounds.
Accordingly, it remains an object of those of skill in the art to establish a method by which cancer metastasis can be prevented or reduced. It is also a goal of those of skill in the art to obtain a method for the treatment and/or removal of heavy metals, radioactive products and the like, without removal of part or all of the blood supply of a patient. It is an additional object of those of skill in the art to find a safe and effective treatment for high circulating values of calcium and other minerals which contribute calcium deposits such as calcinosis (large calcium deposits present in auto-immune condition like dermatomiositis) as well as treating atherosclerosis. A further object of those of skill in the art is to provide a method for treating arteriosclerosis with reduced side effects.